Highly efficient A-to-G base editing by ABE8.17 in rabbits

Area of Science:

• Molecular Biology
• Genetics
• Biotechnology

Background:

• Adenine base editors (ABEs) facilitate precise A-to-G conversions.
• Previous studies noted inefficiency of the ABE7.10 system in challenging rabbit loci.

Purpose of the Study:

• To evaluate the efficacy of novel ABE systems (ABE8.17 and SpRY-ABE8.17) in mouse and rabbit embryos.
• To develop improved base editing tools for generating accurate disease models.

Main Methods:

• Utilized ABE8.17 and SpRY-ABE8.17 systems for base editing in mouse and rabbit embryos.
• Developed a linker-less variant (ABE8.17-NL) for targeted editing.
• Assessed editing efficiency and precision in various cell types and organisms.

Main Results:

• ABE8.17 and SpRY-ABE8.17 demonstrated high efficiency in mouse and rabbit embryos.
• The systems successfully mimicked clinical point mutations in rabbits.
• ABE8.17-NL achieved efficient base editing within a narrower window (2-4 nucleotides) in human cells.

Conclusions:

• ABE8.17 systems offer a significant improvement over ABE7.10 for A-to-G base editing.
• These advanced ABE systems provide an efficient method for generating precise animal disease models, particularly in rabbits.